Radiotherapy is a proven modality for cancer cure similar to surgery for tumors of all sites. The probability to destroy the cancer locally is proportional to the radiation dose delivered to the cancer sites. Most often, the effectiveness of radiotherapy is limited by the radiation dose that can safely be delivered to the normal organs adjacent to the tumor. Serious complications may occur if the normal organs receive a radiation dose that exceeds their tolerance to radiation. Paralysis (spinal cord injury), blindness (optic nerve injury), stroke (brain injury), bleeding (blood vessels injury), inflammation of lungs (lungs injury) and bowels (bowels injury) may lead to death or seriously affect patient quality of life are well known complications of radiation treatment. Current methods of radiation treatments set a maximum limit for the radiation dose.
For example, in Section 6.4.2.4 Radiation Therapy Oncology Group (RTOG) study number 0225: A Phase II Study of Intensity Modulated Radiation Therapy (IMRT)+/Chemotherapy for Nasopharyngeal Cancer, it is specified that “No more than 20% of any PTV70 (the gross tumor volume with a 5 mm margin) will receive ≥110% of the prescribed dose.” The rule limits the toxicity of the treatment to avoid complications.
Referring to FIG. 1B, Tabular Data 1 shows schematic representation of “volumes” in radiation therapy in terms of Gross Target Volume, Clinical Target Volume, Planning Target Volume from Page 5, Chapter 1: The Discipline of Radiation Oncology, Book: Perez and Brady's Principles and Practice of Radiation Oncology, 5th Edition, published by Lippincott Williams & Wilkins with ISBN-10: 078176369X. This figure clearly shows that the planning target volume (PTV) is beyond the tumor boundary.
Tabular Data 2 shows the Memorial Sloan-Kettering Cancer Center (MSKCC) Clinical Dose Limits and Inverse Planning Algorithm Constraints for Primary Nasopharynx Tumors, excerpted from book “A practical guide to intensity-modulated radiation therapy” (Medical Physics Pub., 2003, ISBN: 1930524137), Chapter 10: IMRT for head and neck Cancer, Table 10.3, page 201. The table clearly regulates that the maximum dose is 105%.
TABULAR DATA 2Inverse Plaanning Algorithm Constraint TemplateMaximumMinimumClinical DosePresriptionDose (%)/Dose (%)/Dose (%)-% VolumeStructure LimitsDose (%)PenaltyPenaltyConstraint/PenaltyPTVelD95 ≥ 50 Gy54 Gy (77%)56.7 Gy51.3 GyNA(95% of 54 Gy)(81 %)/50(73%)/50Max. Dose≤64.8 Gy(120% of 54 Gy)PTVgrD95 ≥ 70 Gy70 Gy (100%)66.5 Gy73.5 GyNA(100% of 70 Gy)(105%)/50(95%)/50Max. Dose≤84 Gy(120% of 70 Gy)Spinal CordMax. Dose28 GyNA≤45 Gy(40%)/50BrainstemMax. Dose35 GyNA≤50 Gy(50%)/50ParotidMean Dose68 Gy≥ 21 Gy (30%) toGland≤26 Gy(98%)/50≤30% Volume/50CochleaMax. Dose56 GyNA≤60 Gy(80%)/50
Tabular Data 3 shows the compliance criteria of radiation treatment in Radiation Therapy Oncology Group (RTOG) study number 0920: A Phase III Study of Postoperative Radiation Therapy (IMRT)+/−Cetuximab for Locally-Advanced Resected Head and Neck Cancer, section 6.7, page 27. The criteria lists in Row 1 that any Radiation dose (RT)>66Gy as a major variation should be avoided at any rate. The 66Gy corresponds to a 10% increase over PTV 60Gy.
TABULAR DATA 3Per ProtocolMinor VariationMajor VariationTotal RT dose to PTV6060-64 Gy58-60 or 64-66 Gy<58 or >66 Gy(to 95% of PTV60)Minimum dose (“cold spot” within56-60 Gy54-56 Gy>54 GyPTV60, not including portion ofPTV near (<8 mm) skin)Maximum dose (“hot spot”)<70 Gy70-72 Gy>72 Gywithin PTV60*Maximum dose (“hot spot” outside<66 Gy66-70 Gy>70 Gyof PTV60)Definition of CTV60Base on case review by study chair.Definition of PTV60Base on case review by study chair.Total RT dose to spinal cord PRV<48 Gy48-50 Gy>50 Gy(0.03 cc)Total RT dose to spinal cord PRV <50 Gy50-52 Gy>52 Gy(0.01 cc)Definition of Spinal cord PRVBase on case review by study chair.Overall RT treatment time>50 days (without a medicallyappropriateindication for delay)Non-Medically Indicated0-22-4>4Treatment Interruptions*Not including the region of PTV60 that falls within PTV66 (if applicable)
Tabular Data 4 shows the Critical Normal Structures in Radiation Therapy ONCOLOGY Group (RTOG) study number 0225: A Phase II Study of Intensity Modulated Radiation Therapy (IMRT)+/Chemotherapy for Nasopharyngeal Cancer, section 6.4.3 Critical Normal Structures, page 7. The Critical Normal Structures discloses clearly that 60 Gy or 1% of the PTV cannot exceed 65 Gy (which is close to 10% increase over PTV 60Gy radiation.)
TABULAR DATA 46.4.3Critical Normal StructuresDVH's must be generated for all critical normal structures and the unspecified tissues. Dose constraints to normal tissues will be asfollows:Brainstem, optic nerves, 54 Gy or 1% of the PTVchiasmcannot exceed 60 GySpinal Chord45 Gy or 1 cc (if 1% isused, depends on length of the cord outlined) of thePTV cannot exceed 50 GyMandible and T-M joint70 Gy or 1 cc of the PTVcannot exceed 75 GyTemporal lobes60 Gy or 1% of the PTV cannot exceed 65 GyUnspecified tissue outside the targets: ≤100% of the dose prescribedto PTV70. No more than 5% of the non-target tissue can receive greater than 70 Gy. Participants are strongly encourages to remainwithin these limits.
Tabular Data 5 shows the hotspot radiation regulation in a presentation (slide 13) of a research taken at Dana-Farber/Brigham & Women's Cancer Center and Harvard Medical School (“Variability in planning criteria and plan evaluation”, Laurence Court, the American Association of Physicists in Medicine annual meeting 2010). The slide clearly shows the aiming for hotspots radiation is limited to <110% of the radiation dose.
Tabular Data 5Hotspots105%+ DFCI: Aim for 5%, <110%UMass: aim for <110%. Typically 8% vol < 10%(will accept ~10% of PTV > 110% if necessary)105-110% (MDACC)MGH: 110-115%, 120%+ if necessaryImpact of chemotherapy     AAPM 2010           13
However, the use of a low radiation dose can be ineffective for curing cancer cure and a patient can die from uncontrolled tumor growth or from complications resulting from tumor destruction of the normal organs. Thus, the clinician is often faced with a dilemma: either let the cancer kill the patient or expose the patient to serious injury from radiation complications. Therefore, there is a need for a balanced method for image-guided radiotherapy for providing higher dose for tumor tissues while avoiding excessive radiation to normal tissues. The present invention features a boost dose of radiation with no upper limit and that is applied to both high and low tumor concentrations.
Any feature or combination of features described herein are included within the scope of the present invention provided that the features included in any such combination are not mutually inconsistent as will be apparent from the context, this specification, and the knowledge of one of ordinary skill in the art. Additional advantages and aspects of the present invention are apparent in the following detailed description and claims.